Molecular regulatory mechanisms of Merkel cell differentiation

Merkel cells are specialized oval-shaped epithelial cells located in the basal epidermis and hair follicles, connected with afferent nerve endings responsible for sensory perception of light touch. Recent advances in developmental biology have shed light on the complex regulatory networks governing Merkel cell maturation. The most recent evidence indicates a crosstalk among epigenetic pathways, notably Polycomb multi-subunit complexes, Merkel cell-lineage transcription factors such as atonal BHLH transcription factor 1 (ATOH1), SRY-box transcription factor 2 (SOX2), ISL LIM homeobox 1 (ISL1) and additional players in the regulation of Merkel cell developmental programs. At the same time, the implications of dysregulated Merkel cell-lineage transcription factors during Merkel cell carcinoma (MCC) onset is under investigation. This review offers a comprehensive overview of the current understanding of the genetic and epigenetic pathways crucial for Merkel cell differentiation. It covers the implication of Merkel cell-specific developmental programs, the role of epigenetic regulatory Polycomb complexes, and how genetic and epigenetic mechanisms converge to orchestrate Merkel cell differentiation.